Muscle Function and Animal Handling Core

核心C是动物处理和功能分析核心。该设施位于芝加哥大学。该核心机构将直接从项目（包括巴尔的摩和辛辛那提的项目）接收动物。动物将使用为分析体内肌肉功能而开发的SHIRPA方案的子集进行功能分析。之后，将这些小鼠的材料提供给Core B（组织学核心）进行定量和定性分析。肌营养不良症研究中的一个长期假设是，膜完整性的丧失是导致骨骼肌纤维变性从而导致疾病的主要事件。患病骨骼肌中肌纤维的变性和坏死诱导细胞因子、趋化因子和生长因子从邻近肌纤维、成纤维细胞和炎性细胞释放，所述细胞因子、趋化因子和生长因子渗透到组织中以去除细胞碎片。TGFB和相关的TGPB超家族成员（如肌生长抑制素）的释放参与了这种旁分泌环境，改变了MD中的肌纤维生长、再生和纤维化。肌营养不良症的遗传模型在解剖导致这种疾病并改变其反应的分子效应器方面具有重要意义。该核心将提供这些模型的功能分析，并提供病理分析的材料，以解剖TGFB超家族中编程疾病和纤维化的信号关系。 肌肉萎缩症PPG的所有三个项目将广泛使用转基因小鼠模型来分离单基因功能，以发现新的治疗机会。该项目还将测试新的和现有的药物，以修改这些途径，包括可溶性受体和信号传导抑制剂。本核心将分析这些操作的结果。核心是PPG成功的重要组成部分。

Core C is the Animal Handling and Functional Analysis Core. This facility is located at the University of Chicago. This Core facility will receive animals directly from the Projects, including the Projects in Baltimore and Cincinnati. Animals will undergo functional analysis using a subset of the SHIRPA protocols that were developed for analysis of in vivo muscle function. Following this, materials from these mice will be made available to Core B, the Histopathology Core, for quantitative and qualitative analysis. A longstanding hypothesis in muscular dystrophy research is that loss of membrane integrity is a primary event leading to the degeneration of skeletal muscle fibers resulting in disease. Degeneration and necrosis of myofibers in diseased skeletal muscle induces release of cytokines, chemokines, and growth factors from neighboring myofibers, fibroblasts, and inflammatory cells that infiltrate into the tissue to remove cellular debris. Release of TGFB and related TGPB superfamily members, such as myostatin, is involved in this paracrine milieu that alters both myofiber growth, regeneration, and fibrosis in MD. Genetic models of muscular dystrophy have been of great importance in dissecting the molecular effectors that lead to this disease and alter its response. This core will provide functional analysis of these models and provide materials for pathological analysis to dissect signaling relationships in the TGFB super family in programming disease and fibrosis in muscular dystrophy. All three projects in the PPG will extensively use genetically modified mouse models to isolate single gene function to uncover new therapeutic opportunities. The Projects will also test new and existing drug to modify these pathways including soluble receptor and signaling inhibitors. This Core will analyze the results of these manipulations. The Core is an essential component for the success of the PPG.